PL107647B1 - HOW TO MAKE NEW 1,1-DIOXIDE 4-HYDROXY-2H-NAFTO / 2,1-E / -1.2-Thiazine-3-CARBOXYAMIDE - Google Patents

Description

The subject of the invention is a method for preparing new 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxides and their physiologically acceptable salts with inorganic or organic bases. The new compounds correspond to the general formula I, wherein R1 denotes a hydrogen atom, a methyl or ethyl group and Ar. denotes a phenyl, 3-chlorophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-tolyl, 2-methoxyphenyl, 3-methoxyphenyl, 2-pyridyl, 4-methyl-2-pyridyl, 6-methyl-2-pyridyl, 3-hydroxy-2-pyridyl, 3-pyridyl, 4-pyridyl, 6-chloro-3-pyridazinyl, 2-pyrazinyl, 6-chloro-2-pyrazinyl, 6-chloro-4-pyrimidinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4-ethyl-2-thiazolyl group, 5-methyl-2-thiazolyl, 5-ethyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 4-ethyl-5-methyl-2-thiazolyl, 5-ethyl-4-methyl-2-thiazolyl, 2-benzothiazolyl, 4,5,6,7-tetrahydro-2-benzothiazolyl, 5,6-dihydro-7H-thiopyrano[4,3-d]thiazolyl-2,3-methyl-5-isothiazolyl, 1,3,4-thiadiazolyl, 5-methyl-1,3,4-thiadiazolyl-2 or 5-methyl-3-isoxazolyl. 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxides of general formula I are distinguished by outstanding anti-inflammatory properties and/or exhibit particularly strong inhibiting action on platelet adhesion and aggregation. The compounds of general formula I are prepared by reacting 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ester 1,1-dioxides of general formula II, wherein R5 is an alkyl group having 1-6 carbon atoms or an aralkyl group having 7-10 carbon atoms and R1 has the meaning given above, with an aromatic amine of general formula III, wherein Ar has the meaning given above. The reaction of the carboxylic acid ester of general formula 2 with the aromatic amine of general formula 3 takes place in a suitable inert organic solvent, e.g. in aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene or tetrahydronaphthalene, in dimethylformamide, dimethylacetamide. or dimethyl sulfoxide or in hexamethylphosphoric acid triamide, in ethers such as dimethoxyethane, diethylene glycol methyl ether or diphenyl ether, or also directly in an excess of an aromatic amine. The reaction is carried out at a temperature of 60°C to 200°C. The reaction is preferably carried out in toluene or xylene at boiling temperature, and the alcohol formed during the reaction is removed by azeotropic distillation or by heating under reflux in a Soxlet extractor equipped with a molecular sieve. The product crystallizes directly from the reaction mixture or is obtained by evaporation of the solvent or by precipitation with water. Compounds of general formula 1, wherein R 1 is a methyl or ethyl group, are also prepared by reacting 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid amide 1,1-dioxide of general formula 4, wherein Ar has the meaning given above, with an alkyl halide of general formula 5, wherein Hal is a halogen atom and R' 1 is a methyl or ethyl group, in the presence of a base. Bases used are alkali metal or alkaline earth metal hydroxides, e.g. sodium, potassium or barium hydroxide, or sodium or potassium carbonate, and alkali metal or alkaline earth metal alkoxides, e.g. sodium methoxide, potassium ethoxide, potassium tert. butoxide or A tertiary amine, e.g., triethylamine, if the reaction is carried out in an aqueous medium, an alcoholic medium such as methanol, ethanol, n-propanol, isopropanol, or in mixtures of the solvents mentioned. Other solvents include dimethylformamide, dimethylacetamide, dimethylsulfoxide, and hexamethylphosphoric acid triamide. If an alkali metal or alkaline earth metal carbonate is used as the base, aliphatic ketones such as acetone are used as solvents. The alkyl halide, especially the alkyl bromide or iodide, in alcoholic solution is added directly to the usual components of the reaction mixture, whereas in the case of methyl bromide, the reaction is carried out in a closed apparatus. If the reaction is carried out in an inert organic solvent, such as, for example, benzene or another aromatic hydrocarbon, tetrahydrofuran or another open-chain or cyclic ether, alkali metal or alkaline earth metal hydrides, e.g. sodium hydride or potassium hydride, can also be used as base. The addition of the alkyl halide, however, takes place only when the alkali metal hydride or alkaline earth metal hydride has reacted completely with the starting compound of general formula 4. The reaction temperature is 0-80°C. Compounds of general formula 1, wherein Bi is a methyl or ethyl group and Ar has the meaning given above, are also prepared by reacting an enamino acid chloride of general formula 6, wherein R1 is a methyl or ethyl group, Hal is a halogen atom and R< and R( denote an alkyl group having 1-3 carbon atoms or, together with the nitrogen atom between them, denote a piperidine, pyrrolidine, morpholino or N-methylpiperazine group, with an aromatic amine of general formula 3, wherein Ar has the meaning given above. meaning, and then converting the resulting enaminocarboxamide of general formula 6a by acid hydrolysis into the desired final product. The reaction of the enamino acid chloride of general formula 6 with the amine of general formula 3 takes place in an inert organic solvent, e.g. in an aromatic hydrocarbon or ether, at a temperature from -40° to +80°C and can be carried out in the presence of a tertiary organic base, such as, for example, triethylamine. The hydrolysis is carried out by heating the enaminocarboxamide of general formula 6a with an aqueous or aqueous-alcoholic solution of a strong or medium-strong acid, e.g. hydrohalic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, trifluoroacetic acid or with solutions of strong or medium-strong acids, hydrohalic acids being particularly preferred, in glacial acetic acid or in a mixture of glacial acetic acid and water. The compounds of general formula I can optionally be converted in a known manner into their physiologically compatible salts with inorganic or organic bases. Bases used are, for example, alkali metal alkoxides, alkali metal hydroxides, alkaline earth metal hydroxides, trialkylammonium hydroxides, alkylamines. The ester of general formula II serving as the starting product is obtained from 3-keto-naphtho[2,1-d]isothiazoline 1,1-dioxide (H.P. Kaufmann and H. Zobel, Chem. Ber. 55 (B), 1499 (1922)) by reaction with a solution of an alkali metal alkoxide, removing the alcohol and reacting the resulting 25N alkali metal salt of 3-keto-naphtho[2,1-d]isothiazoline-2-acetic acid alkyl ester 1,1-dioxide in dimethyl sulfoxide with a haloacetic acid ester at a temperature of 120-150°C. The resulting 3-keto-naphtho[2,1-d]isothiazoline-2-acetic acid alkyl ester 1,1-dioxide is subjected to a rearrangement reaction by treatment with 2-3 equivalents of an alkali metal alkoxide and then heating in the presence of a base as a catalyst. After acidification, 4-hydroxy-2H-naphtho[2,1-e]-1,2-acetic acid alkyl ester 1,1-dioxide is obtained. thiazine-3-carboxylic acid of general formula II, wherein R1 is hydrogen. Compounds of general formula II, wherein R1 is methyl or ethyl, are obtained by alkylation with a methyl or ethyl halide, e.g. methyl or ethyl iodide, in an alcoholic or aqueous-alcoholic solvent, using an equivalent amount of alkali metal hydroxide. Aromatic amines of general formula III, with the exception of those given below, are generally known. 2-amino-5-methyl-thiazole and 2-amino-5-ethyl-thiazole are prepared according to the instructions given by H. Erlenmeyer, L. Herzfeld and B. Prijs (Helv. Chem. Acta 38, 1291). (1955). 2-amino-4,5,6,7-tetrahydro-benzothiazole is prepared by the L.C. method. King and R.J. Hlavacek (J. Amer.Chem. Soc. 72, 3722 (1950)), and 2-amino-4-ethyl-thiazole, 2-amino-4-ethyl-5-methyl-thiazole, 2-amino-5-ethyl-4-55-methyl-thiazole and 2-amino-5,5-dihydro-7H-thiopyra- no[4,3-d]thiazole is prepared analogously. The starting compounds of the general formula 4 are obtained from 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ester 1,1-dioxide according to the above-described The starting compounds of general formula 6 are prepared, for example, by reacting 2H-naphtho[2,1-e]-1,2-thiazin-4(3H)-one 1,1-dioxide of general formula 8 with a secondary aliphatic amine of general formula 6B9, wherein R< and R* have the meaning given above.5 107 647 6 in an organic inert solvent in the presence of an acid catalyst, and the resulting compound of general formula 10, wherein R< and R<' have the meaning given above and R'' is a methyl or ethyl group, is then treated with phosgene in the presence of a tertiary organic base, such as, for example, triethylamine, in an inert organic solvent, for example, tetrahydrofuran, at a temperature of from -50° to +30°C. +50°C. The resulting enamino acid chloride of general formula (VI) can be used directly, especially without isolation. V As already mentioned, the compounds of general formula (I) have valuable pharmacological properties; they have an anti-inflammatory effect and/or strongly inhibit platelet adhesion and aggregation. Consequently, they have a beneficial effect in all kinds of rheumatic diseases, e.g. in arthritic conditions. The following substance was tested as an example: A = 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide, compared with the known indomethacin: B = (indomethacin acid) 5-methoxy-2-methyl-1-(4-chloro-benzoyl)-3-indole acetic acid), on their anti-exudative effect on kaolin-induced edema and carrageenan-induced edema on the hind paws of rats, and on their acute toxicity after an oral dose administered to rats, a) Kaolin edema on the hind paw rat: Edema was induced according to Hillebrechf (Arzneimittel-Forsch. 4, 607 (1954)) by subplantar injection of 0.05 ml of a 10% suspension of kaolin in a 0.85% NaCl solution. The paw thickness was measured using the Doepfner and Cerletti method (Int. Arch. Allergy Immunol. 12, 89 (1958)). Male FW 49 rats weighing 120-150 g were given the test substance. The dose leading to a 35% reduction in edema (EDu) was determined. b) Carrageenan edema on the rat hind paw: The edema was induced according to the data of Winter et al. (Proc. Soc. exp. Biol. Med. 111, 544 (1962)) by subplantar injection of 0.05 ml of a 1/2 e carrageenan solution in 0.85% NaCl solution. The test substance was administered 60 minutes before edema induction. To assess the edema-inhibiting effect, measurements were carried out 3 hours after edema induction, proceeding as described for kaolin edema. c) Acute toxicity: The LDh value was determined after oral administration to male and female (in equal amounts) FW '49 rats with an average weight of 135 g. The test substance was administered ground with Tylose. The LDM value was calculated, if possible, using the Lichtfield and Wilcoxon method, from the percentage of animals that died within 14 days after receiving various doses. The therapeutic index, as a measure of the therapeutic range, was calculated by creating a quotient of the DLM (oral) and the ED« obtained in the tests for anti-exudative effect (average value of the calcium and carrageenan tests). The results obtained in these tests are summarized in the following table. The tested compound is twice as good as the known indomethacin in terms of its therapeutic range. In addition, e.g. compound A and compound C, 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide, were tested for their antiarthritic (Adjuvansarthritis) activity in rats and compared in this respect with phenylbutazone (1,2-diphenyl- Substance B* A Kaolin edema ED35 oral mg)fcg 2.7 13.5 Carrageenan edema ED35 oral 2.9 11 Mean value EDjb mg/kg 2.8 12.2 Acute toxicity in rats oral LD50 mg/kg 25.7 207 Permissible limits at 95*/« probability 2(1.8—30.3 126—265 Therapeutic index, Ratio of toxic and anti-inflammatory effects LD$0/ED,6 2.2 16.9 B*=reference substance 30 minutes before induction of edema by means of an esophageal tube. 5 hours after induction of edema, the mean swelling values in animals treated with the test substance were compared with those in control animals. By graphical extrapolation of the percentage inhibition values, the results were obtained. d) Arthritis (Adjuvansarthritis) in rats: The studies on anti-arthritic activity in rats were carried out according to the data of Rosethale and Nagra. (Proc. Soc. exp. Biol. Med. 125, 149 (1967)). Male FW 49" rats from our own breeding farm received a small 0.1 ml 1/2 suspension of M. butyricum in viscous paraffin oil, injected subplantarly into the hind paw. The substances to be tested were introduced daily for 20 days, starting from the day of injection, by means of an esophageal gavage. On the 21st day after the induction of arthritis symptoms, the volumes of the right paw (nonspecific primary reaction at the injection site) and the left paw (immunologically determined specific secondary reaction) of the animals treated with the test substance were compared with the volumes of the paws of the control animals, treated sham-treated. Based on the reduction in swelling achieved with different doses, the EDB0 was determined graphically. The results obtained in these studies are given in the following table. Substance D* A C Arthritis (Ajuvansarthritis) in rats (average value of the primary and secondary reaction) ED50 oral mg/kg —40 <2 | ~ 4 1 D* = reference substance As can be seen from the table, substances A and C show unexpectedly strong, as indicated by the results of tests on paw swelling, action on arthritis induced in rats. Both compounds are many times more effective than the well-known anti-inflammatory agent phenylbutazone. Compound A was tested for its inhibitory effect on the adhesion and aggregation of human blood platelets and compared with the compound E known from DAS No. 2 208 351: E = 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (Sudoxilam). These tests were carried out using the following two tests: a) Morris test The principle of the Morris test is described in "Stoffwechsel- und Membranpermeabulitat von Erythrozyten und Thrombozyten", I. Int. Symposium in Wien, 17-22 June 1968, Georg-Thieme-Verlag, Stuttgart": 1 ml of citrated whole blood was pipetted into small test tubes, to which the test substances were added at the given concentrations and incubated for 10 minutes at 37°C. To half of the tubes, 2 g of glass beads (BDH, Poole, England) were added. The tubes, closed with plastic stoppers, were mounted on a vertically placed disk and rotated end-over-end for 45 seconds. Blood was left in the same tubes for 1 hour at room temperature. During this time, the erythrocytes and glass beads sedimented. A 1 ml sample was taken from the superficial plasma and diluted with the celloscopic solution in a ratio of 1:8000. Platelets were counted in the celloscope. The difference in the number of platelets in contact with and not in contact with the glass beads was used to calculate the number of platelets adhered or aggregated on the glass beads during sedimentation. The following table shows the percentage reduction in viscosity compared to the control samples (without the addition of the test substance). b) Born test, collagen aggregation. Platelet aggregation was measured by the method of Born and Gross (J. Physiol. 170, 397 (1964) on platelet-rich plasma from healthy individuals. The reduction in the optical density of the platelet suspension after the addition of collagen was measured photometrically and recorded. The aggregation velocity is derived from the angle of the density curve. The point on the curve at which the highest light transmittance occurs is used to calculate the "optical density". The amount of collagen is selected so that an irreversible curve is formed. The figures given refer to the "optical density" and indicate the percentage changes in light transmittance (=% reduction in aggregation) under the influence of the test substance compared to the control samples. ^ Commercial collagen from Hormon-Chemie, Munich, was used in the tests. The following table shows the results obtained in both tests. Substance A E* Concentration (mjoyi) io-* io-1 io-e io-7 io-* io-8 io-6 Morris test 43% 3% Born test mg/kg 96% 95% 92% 65% 92%! 91%' 93% Acute toxicity (rats) LDbo oral mg/kg 207.0 136.0 Permissible limits with 95% probability 126.2—265.0 104.6—176.8 = reference substance 107 647 10 As can be seen from this table, substance A, in comparison to substance E, has a stronger inhibitory effect on platelet aggregation. Substance A causes a 50% reduction in aggregation even at a concentration significantly lower than that of substance E. The inhibition of adhesion by substance E in the Morris test by only 3% means that substance E, in contrast to substance A, is practically inactive. Furthermore, substance A is less toxic than substance E. Furthermore, the following substances were tested for their inhibitory effect on platelet aggregation (Born test, collagen aggregation), as an example: v F = N-(3-chlorophenyl)-4-hydroxy-2-1,1-dioxide -methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide G=1,1-dioxide 4-hydroxy-2-methylI-N-(3-clyl)- -2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide H=sodium salt of 1,1-dioxide 4-hydroxy-2-methyl- -N-(4-methyl-2-pyridyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide ¦1=1,1-dioxide N-(6-chloro-2-pyrazinyl)-4-hydro- xy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide J=1,1-dioxide 4-hydroxy-2-methyl-N-(4-methyl-2-thiazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide K=1,1-dioxide 4-hydroxy-2-methyl-N-(5-methyl- lo-2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide M=1,1-dioxide N-(4-ethyl-5-methyl-2-thiazolyl)- -4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide N=acetylsalicylic acid as a reference compound. The following table presents the results of the tests carried out: Substance 1 F G H I J Concentration (mol/l) Born test | 2 | 3 1 10~4 10-5 10-6 10~4 10-5 10-6 10~4 10-5 10-6 IG"5 10-6 10-7 10~4 10-5 10-6 I-O"7 96% 81% 35% 97% 78% 65% 95% 91% 82% 91% ^91% ^2% 92% 89% 88% - ¦'. 4% . . 10 15 30 35 40 45 50 80 1 1 K L M N* 2 10~4 10-5 10-6 10~4 10-5 10-6 10-7 10-* 10-5 10-6 10-7 3. 10-5 10"5 3 89% 97% 66% 91% 95% 88% 15% . 94% 91% 79% 24% . 45% 13% 20 N*=reference substance While the reference substance N (acetylsalicylic acid) achieves a 50% reduction in aggregation only at a concentration of 4.10-5 mol/l, substances H, I, J, L and M cause a 50% reduction aggregation at a concentration at least two times lower, and substances F, G and K at a concentration at least 20 times lower. The new compounds of general formula I can be processed for pharmaceutical use, alone or in combination with other active substances of general formula I, into pharmaceutical preparations. The unit dose is 10-250 mg, especially 25-100 mg, the daily dose is 25-500 mg, especially 50-250 mg. The following examples explain the invention in more detail without limiting its scope. Example 1. N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 9.58 g (0.03 mole) of 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 5.1 g (0.04 mole) of 3-chloroaniline are heated in 400 ml of anhydrous xylene for 24 hours under reflux in a Soxlet apparatus filled with 4-A molecular sieves. After cooling and standing overnight, the crystals are filtered off. After recrystallization from ethylene chloride, 9.1 g (73% of theory) of N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1-dioxide are obtained, m.p. melting point: 248—249°C. The starting compound is obtained by replacing intermediate stages: a) 3-keto-naphtho[2,1-e]isothiazoline-2-acetic acid methyl ester 1,1-dioxide. To a solution of 7.82 g (0.34 gram atoms) of sodium in 300 ml of absolute methanol is added 70.0 g (0.30 moles) of 3-keto-naphtho[2,1-d]isothiazoline-1,1-dioxide. Then the alcohol is distilled off to a high degree and the remaining sodium salt of 3-keto-naphtho[2,1-d]isothiazoline-1-,1-dioxide is dissolved in 100 ml of dimethyl sulfoxide. Then 43.41 g (0.40 mol) of chloroacetic acid methyl ester were added dropwise to this solution at 50°C. The mixture was stirred for half an hour at room temperature, then slowly heated to 130°C and kept at this temperature for 2.5 hours. The dimethyl sulfoxide was then distilled off in vacuo. The residue was stirred with a solution of 40 g of sodium acetate in 400 ml of water, filtered and washed with water and ice-cold methanol. 90.0 g (98% of theory) of 3-keto-naphtho[2,1-d]isothiazolin-2-acetic acid methyl ester, 1,1-dioxide, was obtained. Melting point: 188°C (methanol/ethylene chloride). I b) 4-hydroxy-2H-naphtho[2,1-d]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 0.90 mol of alcohol-free sodium methoxide are prepared by dissolving 20.7 g (0.90 gram atom) of sodium in 350 ml of absolute methanol, distilling off the alcohol and again azeotroping with xylene. After adding 91.5 g (0.30 mol) of 3-keto-naphtho[2,1-d]isothiazolin-2-acetic acid methyl ester 1,1-dioxide, 250 ml of anhydrous tert.-butanol are added. The reaction mixture was slowly heated to 60°C, kept for 1 1/4 hours at 60-65°C, then heated to reflux for 1 hour. It was cooled, decomposed with ice, and the mixture was adjusted to a pfi of 3-4 with concentrated hydrochloric acid. The precipitated product was filtered off, washed with water, and dried. Yield: 72.0 g (78% of theory) of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester, 1,1-dioxide, melting point: 216-220°C (after twice recrystallization from ethylene chloride). c) 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide To a suspension of 61.0 g (0.2 mol) of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 85.1 g (0.6 mol) of methyl iodide in 500 ml of methanol is added dropwise over 40 minutes, while the reaction temperature is maintained at 20-25°C. After stirring for 4 hours, the solution is cooled to +5°C, the precipitate is (=50 g of crude product) is filtered off and washed with ice-cold methanol. The combined filtrates are heated to 40°C for 15 minutes and concentrated in vacuo until crystallization begins. Filtration and washing with ice-cold methanol gives a further 9 g of crude product. Recrystallization of the combined crude product from ethylene chloride gives 53.3 g (85% of theory) of 4-hydroxy-2-methyl-2H-naphtho[-2,1-e]thiazine-3-carboxylic acid methyl ester, 1,1-dioxide, melting point: 229-2309°C. Example II. 4-Hydroxy-2-methyl-2H-naphtho[-2,1-e]thiazine-3-carboxylic acid methyl ester, 1,1-dioxide tyl-N-phenyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide - Prepared analogously to example 1 from 4-hydroxy-2-methyl-2H-naphtho[2,1-eI-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and aniline, with a yield of 69°/# of theoretical yield. Melting point: 273-274°C (decomposition) from ethylene chloride. Example III. N-(3-bromophenyslo)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to example 1 from ester 1,1-dioxide methyl 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and bromoaniline in toluene with a yield of 77% of the theoretical yield. Melting point: 268-269°C (decomposition) from xylene. EXAMPLE IV. N-(2-fluorophenyl)-4-hydroxy-2-methyl-2H-naphto[2,1-e]-1,2-thiazine-3-11 carboxamide 1,1-dioxide. It is prepared analogously to Example 1 from 4-hydro-1,1-methyl ester 1,1-dioxide xy-2-methyl-2H-naphtho{2,l-e]-i;2-thiaz3«K-3-carboxylic acid and 2-fluoroaniline with yields equal to the theoretical yield. Melting point: 240-243°C (decomposition) from xylene. Example Y. 1,1-dioxide N-(3-fluorophenyl)-4-hydroxy-2rmethyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 25 Prepared analogously to example I from 1,1-dioxide 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester and 3-fluoroaniline with yield B9*/yield theoretical. Melting point and 278-279°C (decomposition) from xylene. Example VI. N-(4-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example J 95 from 4-hydroxy-methyl ester 1,1-dioxide xy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazines-3-carboxylic acid and 4-fluoroaniline with a yield of 89% of the theoretical yield. Melting point: 284-285°C (decomposition) from xylene. ia Example VII. 1,1-dioxide 4-hydroxy-2- -methyl-N-(3-tolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide Prepared analogously to example 1 from 4-hydroxy-2-methyl-2H-naphtho[2,l-e]-l,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide xylic acid and m-toluidine with a yield of 65% of the theoretical yield. Melting point: 240-242°C (decomposition) from xylene. Example VIII. 4-hydroxy-N-M-(2-methoxyphenyl)-2-methyl-2H-naphtho[2,1-e]-1,2-thia-" zine-3-carboxamide 1,1-dioxide. Prepared analogously to in Example I from 4-hydroxy-2-methyl-2H-naphtho[211-e]-112-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-menthoxyaniline in a yield of 0.31% of the theory. Melting point: 198-200°C from ethylene chloride/petroleum ether. Example IX 4-hydroxy-N-(3-methoxyphenyl)-2-methyl-2H-naphtho[211-e]-112-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-menthoxyaniline in a yield of 0.31% of the theory. Melting point: 198-200°C from ethylene chloride/petroleum ether. o-3-carboxamide "^ It is prepared analogously to example I from 1,1-dioxide of 4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid methyl ester and 3-mentoxyaniline with a yield of -1S 107*47 14 82*/t theoretical yield. Melting point: 242-244°C (decomposition) from xylene. Example moles) of acid methyl ester 1,1-dioxide 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 3.8 g (0.04 mol) of 2-amino-pyridine are heated in 250 ml of anhydrous xylene for 14 hours under reflux in a Soxlet apparatus filled with a molecular sieve. 4-A. After cooling and standing overnight, the crystals are filtered off and recrystallized from ethylene chloride. 5.4 g (42%/t theoretical yield) of crystals of the title compound are obtained. Melting point: 237-238°C (decomposition). Example XI. 1,1-dioxide 4-hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-naphtho[2,1re]-1,2-thiazine-3-carboxamide 5.0 g (0.016 mol) acid methyl ester 1,1-dioxide 4-Hydroxy-2-methyl-2H-naphtha2,1-eJ-1,2-, thiazine-3-carboxamide and 2.2 g (0.02 mol) of 2-amino-4-methyl-pyridine in 220 ml of xylene are reacted in the same way as in Example X. After recrystallization from ethyl acetate, 3.5 g (58*/t theoretical yield) of 1,1-dioxide are obtained 4-hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazinecarboxamide* Melting point: 221°C (decomposition). Example XII. 4-hydroxy-2-methyl-2-methyl-2-pyridyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example sy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-6-methyl-pyridine with a yield of 51%/t theoretical yield. Melting point: 221-223°C (decomposition) from ethyl acetate. Example XIII. 4-hydroxy-N-(3-hydroxy-2-pyridyl)-2-methyl-2H-naito[2,l-e]- -l,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example T from 1,1-dioxide of 4-hydro- xy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-3-hydroxy-pyridine with a yield of 40%/t of theoretical yield. Melting point: 255°C (decomposition). Example XIV. 1,1-dioxide 4-hydroxy-2- -methyl-N-(3-pyridyl)-2H-naphtho{2,1-e]-1,2-thiazine-3-carboxamide - Prepared analogously to Example I from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide methyl ester 1,1-dioxide xylic acid and 3-aminopyridine with a yield of 59M theoretical yield. Melting point: 254°C (decomposition) from ethanol/ethyl acetate.P r-z; C l a d e XV. 1,1-dioxide 4-hydroxy-2-me^ib^-N^i-pyridyl^H-naphtho^^-el-l^-thiazine- Hydroxyamide is prepared analogously to Example I from 4-hydroxy-2-methylp-2H-naphtho[2.1-eJ-1,2-thiazirid-3-carboxylic acid methyl ester dioxide and 4-aminopyridine with a yield of 55%/t theoretical efficiency. Melting point: 257°C (decomposition) from ethanol. Example XVI. N-(6-chloro-3-pyridazinol)-4-hydroxy-2-methyl-2H-naito[2,l-e]- s 1,2-thiazines-3-carboxamide 1,1-dioxide 3.2 g (0.01 mol) acid methyl ester 1,1-dioxide 4-Hydroxy-2-methyl-2H-naphtho[2,1-eJ-1,2-thiazine-3-carboxylic acid with 1.7 g (0.013) mol) of 3-amino-6-chloropyridazine is heated in 200 ml of anhydrous xylene for 60 hours under reflux in a Soxlet apparatus filled with 4-A molecular sieves. After cooling and concentration to a syrupy consistency, it is purified on a silica gel column (Merck-Kieselgel fur die Saulenchromatographie 0.2-0.5 mm), using chloroform/methanol (95:5) as eluent. 1.4 g (34% of theoretical yield) of 1,1-dioxide are obtained. N-(6-chloro-3-pyridazinyl)-4-hydroxy-2-n*ethyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide, at melting point: 235-237°C (decomposition). Example XVII 1,1-dioxide 4-hydroxy-2- methyl^N-pyrazinyl*2H-naphtho[2,1^e]-1,2-thiazine-3-carboxamide 4.8 g 2.1 g (0.022 mol) aminopyrazine in 200 ml of dry xylene in the apparatus Then another 0.5 g of aminopyrazine was added, heated for a further 8 hours under reflux, cooled and left overnight, the precipitate was filtered off and the filtrate was evaporated in vacuo. The combined solids were recrystallized from ethyl acetate to obtain 3.0 g (52% of theory) of 4-hydroxy-2-methyl-N-pyrazinyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Melting point: 245°C (decomposition). Example XVIII. N-(6-chloro-)-1,1-dioxide -2-pyrazinyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-eJ- 1,2-thiazine-3-carboxamide. Prepared analogously to Example I from 4-hydroxy-2-methyl-2H-naito[2,l-e]-1,2-thiazine-3-carboxamide methyl ester 1,1-dioxide 45 xylic acid and 2-amino-6-chloropyrazine with a yield of 46% of the theoretical yield. Melting point: 209-210°C (from ethanol). Example XIX. 1,1-dioxide N-(6-chloro-4-, pyrimidinyl)-4-hydroxy-2-methyl-2H-naphtho{2,l-e]- 50 1,2-thiazine-3-carboxamide It is prepared analogously to example I from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 4-amino-6-chloropyrimidine with a yield of 47*/« theoretical yield. Melting point: 263°C (decomposition) from xylene. Example XX. 4-hydroxy-,-2-methyl-N-(2-thiazolyl)-2H-naphtho[2jl-e]-1,2-thiazine-3-carboxamide 1,1-dioxide M 19.8 g (0.062 mol) ester 1,1-dioxide 4-hydroxy-2-methyl-2H-naphthot-2,1-e]^1,2-thiazine-3-carboxylic acid methyl and 9.3 g (0.093 mol) of 2-ainine-thiazoium in 500 ml of xylene are reacted analogously to Example I. After recrystallization from ethylene chloride, 13.5 g107 647 15 16 (56% of theoretical yield) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide are obtained. Melting point: 248-249°C (decomposition). Example XXI. 1,1-dioxide 4-hydroxy-2- methyl-N-(4-methyl-2-thiazolyl)-2H-naphtho[2,l-e]-1,2- thiazine-3-carboxamide 5.0 g (0.016 mol) 4-hydroxy-2-methyl-2H-naphtho[2,1 -e]-1,2-thia-methyl ester 1,1-dioxide zinc-3-carboxylic acid is reacted with 2.75 g (0.025 mol) of 2-amino-4-methyl-thiazole in 200 ml of xylene analogously to Example I. 2.52 g (40% of theoretical yield) of 1,1-dioxide are obtained 4-hydroxy-2-methyl-N-(4-methyl-N-(4- methyl-2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-k'a*r-boxamide. Melting point: 177°C with decomposition (from ethyl acetate). Example XXII. N-(4-ethyl-2-thiazolyl)-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 8 g (0.025 mol) acid methyl ester 1,1-dioxide 4-hydroxy-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 3.8 g (0.03 mol) 2-amino-4-ethyl-thiazole in 500 ml of dry xylene are heated for 24 hours under reflux in a Soxlet apparatus filled with 4-A molecular sieves. The reaction mixture is filtered hot and after cooling and standing overnight, the crystals formed are filtered off. Further crystals are obtained from the mother liquor by concentration. Recrystallization from xylene-ether gives 6.6 g (64% of theory) of N-(4-ethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1^-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Melting point: 194-195°C. The 2-amino-4-ethyl-thiazole used is obtained in the following general way: v a) substituted 2-Aminothiazole, 0.5 moles of alkyl ketone, 0.5 moles of iodine and 1 mole of urea are mixed together and heated for 15 hours to 100°C. The reaction mixture is stirred with hot water and the insoluble particles are filtered off. On cooling the aqueous solution, the hydroiodide of the substituted 2-aminothiazole crystallizes, from which the amine is liberated with concentrated ammonia. In this way, 2-amino-4-ethyl-5-methyl-thiazole is obtained from diethyl ketone (melting point: 72°C, yield = 70% of theory), and 2-amino-5,6-dihydro-7H-topyrano(4,3-d)-thiazole is obtained from tetrahydrothiopyranone-4 (melting point: 170-172°C, yield: 64% of theory), from ethylmethylketone a mixture of 2-amino-4,5-dimethylthiazole and 2-amino-4-ethylthiazole is obtained, from which 2-amino-4-ethylthiazole (melting point: 36°C, yield: 20% of theory) is isolated by column chromatography (eluent: chloroform - ethanol, 95:5, the isomer with the higher Rf value is the desired compound), and from methylpropylketone a mixture of 2-amino-5-ethyl-4-methylthiazole and 2-amino-4-propylthiazole, from which 2-amino-5-ethyl-4-methylthiazole is isolated (syrup, hydrochloride melting point: 179-180°C, yield: 58% of theory) also by column chromatography (eluent: chloroform/ethanol, 95:5, the isomer with the lower Rf value is the desired compound). Separation of the isomers is carried out by fractional precipitation of the hydrochlorides or by fractional crystallization of the hydroiodides. Example XXIII 4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 10 Prepared analogously to Example XXII from 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide methyl ester 1,1-dioxide -methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-5-methylthiazole with a yield of 67% of the theoretical yield. 15 Melting point: 249-250°C (decomposition) from xylene. . ¦ ' Example XXIV. N-(5-ethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 20 Prepared analogously to Example XXII from 1,1-dioxide of 4-acid methyl ester -hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid and 2-Amino-5-ethylthiazole in a yield of 54% of theory. Melting point: 230°C (decomposition) from xylene. Example XXV N-(4,5-Dimethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide Prepared analogously to Example 22 from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-amino-4,5-dimethylthiazole in a yield of 31% of theory. Melting point: 264-265°C (decomposition) 35 from ethylene chloride. Example XXVI. N-(4-ethyl-5-methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example XXII from 4-acid methyl ester 1,1-dioxide hydroxy-2-methyl-2H-naphtho[»,1-e]-1,2-thiazine-3-carboxylic acid with a yield of 45% of the theoretical yield. Melting point: 233-234°C (decomposition) from xylene. Example XXVII. 1,1-dioxide N-(5-ethyl-4- methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide. Prepared analogously to Example XXII from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-methyl ester 1,1-dioxide carboxylic acid and 2-amino-5-ethyl-4-methyl-thiazole with a yield of 63% of the theoretical yield. Melting point: 253-255°C (decomposition) from ethanol. Example XXVIII. 1,1-dioxide N-(2-benzothiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine -3-Carboxamide Vv7y is prepared analogously to Example XXII from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-aminobenzothiazole. Yield: 70% of theory. Melting point: 262°C (decomposition) from xylene. Example XXIX. 4-hydroxy-2-1,1-dioxide 45107447 17 18 methyl-N-(4,56,7-tetrahydro-2-benzothiazolyl)-2H- naphtho[2,1-e]-1,2-thiazine-3-carboxamide Preparation analogously to Example XXII from 1,1-dioxide ester methyl 4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid and 2-amino-4,5,6,7-tetrahydro-benzothiazole with a yield of 38% of the theoretical yield. Melting point: 255-257°C (decomposition) from ethylene chloride. Example XXX. N-(5,6-dihydro-7H-thiopyrano[4,3-d]-thiazo-2-yl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example XXII from methyl ester 1,1-dioxide 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2thiazine-3-carboxylic acid and 2-amino-5,6-dihydro-7H-thiopyrano[4,3-d]-thiazole with a yield of 67% of the theoretical yield. Melting point: 255°C (decomposition) with xylene. Example 31. 1,1-dioxide 4-hydroxy-2-methyl-N-(3-methyl-5-isothiazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide Prepared analogously to Example XXII from acid methyl ester 1,1-dioxide 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 5-amino-3-methylisothiazole with a yield of 44% of the theoretical yield. Melting point: 268°C (decomposition) from ethylene chloride. Example XXXII. 1,1-dioxide 4-hydroxy-2-methyl-N-(1,3,4-thiadiazolyl)-2H-naphtho[2,l-e]-1,2-thia- zine-3-carboxamide It is prepared analogously to example I from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-amino-1,3,4-thiadiazole with a yield of 41%. theoretical efficiency. Melting point: 217-219°C (decomposition) from ethylene chloride and ethyl acetate. Example XXXIII. i,l-dioxide 4-hydroxy-2-methyl-N-(5-methyl-1,3,4-thiadiazol-2-yl)-2H-naphthó[2,l-e]-1,2-thiazine-3-l§arboxamide. Prepared analogously to Example I from 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-amino-5-methyl-1,3,4-thiadiazole with a yield of 21% of the theoretical yield. Temperature melting point: 252-255°C (decomposition) from ethanol. Example XXXIV. 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 4.3 g (0.015 mol) acid methyl ester 1,1-dioxide 4-Hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid is reacted with 2.11 g (0.021 mol) of 3-amino-5-methyl-isoxazole in 250 ml of dry xylene analogously to Example I. After recrystallization from xylene, the product is obtained 3.3 -g (57% of theoretical yield) 4-hydroxy-2-methyl-N-(5-methyl-3-iso-azoyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxy-aryide 1,1-dioxide, melting point: 253°C. Example XXXV. -1,1-dioxide 4-hydroxy- N-phenyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 9.58 g (0.03 mol) 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-5 carboxylic acid methyl ester 1,1-dioxide and 3.72 g (0.04 moles) of aniline are heated in 150 ml of anhydrous xylene for 10 hours in a soxlet apparatus filled with a 4-A molecular sieve, under a reflux condenser. After cooling, the mixture was left to stand overnight, the precipitated crystals were filtered off and recrystallized from ethylene chloride. 6.10 g (55% of theory) of 4-hydroxy-N-phenyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide were obtained. Melting point: 260-262°C. Example XXXVI N-(3^chloro-phenyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide N 1 g (3.3 mmol) 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-car-20 methyl ester 1,1-dioxide boxyl acid and 0.5 g (4 mmol) of 3-chloroaniline are heated in 200 ml of anhydrous xylene for 25 hours in a soxlet apparatus filled with 4-A molecular sieve, under reflux. On cooling, the reaction product crystallizes. 0.9 g (68% of theory) of the end product was obtained, melting point: 262°C (decomposition). Example XXXVII 4-Hydroxy-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 3.2 g (0.01 mol) of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 1.5 g (0.015 mol) of 2-aminothiazole were heated in 200 ml of dry xylene analogously to Example XXXV for 16 hours. After cooling, the precipitate was filtered off and the mother liquor was concentrated in vacuo to give a further amount of crude 4-hydroxy-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. The two fractions were combined and recrystallized three times from acetonitrile. Yield: 0.85 g (23% of theory), melting point: 238°C (decomposition). Example XXXVIII. N-(4,5-dimethyl-2-thiazolyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example XXXVII from acid methyl ester 1,1-dioxide 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-4,5-dimethyl-thiazole in a yield of 35% of the theoretical yield. Melting point: 253° C. (decomposition, from xylene. Example XXXIX. 1,1-dioxide N-(4-ethyl-5- methyl-2-thiazolyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide. Prepared analogously to Example XXXVII from 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-amino-4-ethyl-5-methyl-thiazole with a yield of 55% of the theoretical yield. Melting point: 268-270°C (decomposition) from xylene. Example XL. 2-ethyl-4-hydroxy-N-phenyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 1.65 g (5 mmol) of 2-ethyl-4-hydroxy-2H-naphtho[2,l-e]-1,2-thiazy-30 35 45 50 50 6019 107 647 20 methyl ester 1,1-dioxide and 0.56 g (6 mmol) of aniline are heated in 150 ml of anhydrous xylene for 24 hours in a soxlet apparatus filled with a 4-A molecular sieve under a reflux condenser. From the cooled reaction mixture, 1.8 g (90% of theoretical yield) of 2-ethyl-4-hydroxy-N-phenyl-2H-naphtho[2,l-e]-i,2-thiazine-3-1,1-dioxide crystallize. carboxamide, melting point: 245-247°C (xylene). The starting compound is obtained as follows: 2-ethyl-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 11-dioxide. To a suspension of 10.1 g (0.033 mol) of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 20 g (0.12 mol) of ethyl iodide in 400 ml of 75% aqueous ether solution, 33 ml of 1 N sodium hydroxide are added dropwise over 25 minutes, whereupon the starting product dissolves completely. The reaction mixture was then stirred for 30 hours at room temperature. The crystallized product was filtered off and washed with a small amount of ethanol. 8.7 g of product were obtained (79% of theory). Melting point: 179°C (ethanol). Example 41: 2-Ethyl-4-hydroxy-N-(2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. The product was prepared analogously to Example 41 from 2-ethyl-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 2-aminopyridine in a yield of 86%. Theoretical yield. Melting point: 230-231°C (from xylene). Example 42. 2-Ethyl-4-hydroxy-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. 3.3 g (0.01 mol) of 2-ethyl-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide and 1.5 g (0.015 mol) of 2-aminothiazole were reacted in 150 ml of xylene in a similar manner as in Example 41. After recrystallization from ethyl acetate, 1.0 g (25% of theoretical yield) was obtained. 2-ethyl-4-hydroxy-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide, melting point: 261-262°C (decomposition). Example XLIII. N-(3-chlorophenyl)-=4-hydroxy-2-methyl-2H-naphtho[2,1-e-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example I from 1,1-dioxide of 4-hydro- xy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid and 3-chloroaniline with a yield of 71% of the theoretical yield. Melting point: 248-249°C (decomposition) from ethylene chloride. The starting product is prepared as follows: a) 3-keto-naphtho[2,1-d]-isothiazoline-2-acetic acid ethyl ester 1,1-dioxide Prepared analogously to Example 1 under a) from the sodium salt of 3-keto-naphtho[2,1-d]isothiazoline-1,1-dioxide and chloroacetic acid ethyl ester in a yield of 72% of theory. Melting point: 149-150.5°C (from ethanol). b) 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ethyl ester 1,1-dioxide 4.2 g (0.18 gram atoms) of sodium are dissolved in 100 ml of ethanol. After adding 23.1 g (0.072 mmol) of 3-keto-naphtho[2.1-d]isothiazoline-2-acetic acid 1,1-ethyl ester, the mixture is heated to a temperature of 60-65° C. for 2 hours and treated in the same way as in Example I under b). 9.7 g (42% of theory) of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ethyl ester 1,1-dioxide were obtained, melting point: 202-204°C from ethanol. c) 4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ethyl ester 1,1-dioxide The preparation was carried out analogously to Example 1, c) from 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ethyl ester 1,1-dioxide and methyl iodide. Yield: 82% of theory, melting point: 163—165°C. Example XLIV. N-(4-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example I from 4-hydroxy-2-methyl- n-butyl ester 2H-naphtho-[2,1-e]-1,2-thiazine-3-carboxylic acid (melting point: 159-161°C from a mixture of carbon tetrachloride and ethyl alcohol) and 4-fluoroaniline in xylene, (reaction time: 48 hours). The yield is 72% of the theoretical yield. Melting point: 284-285°C (decomposition) from xylene. Example XLV. N-(4-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide Prepared analogously to Example 1 from 4-hydroxy-2-methyl-2H-[2,1-e]-1,2-thiazine-3-carboxylic acid benzyl ester (mp: 159-161°C from a mixture of carbon tetrachloride and ethyl alcohol) and 4-fluoroaniline in xylene (reaction time: 48 hours). Yield: 72% of theory. Melting point: 284-285°C (decomposition) from xylene. Example 46. N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide For suspension 1.2 g (3 mmol) N-1,1-dioxide -(3-chlorophenyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide, 100 ml of methanol and 1.7 g (12 mmol) of methyl iodide are added dropwise with 3.15 ml of sodium hydroxide solution (3.15 mmol). The reaction mixture is left to stand for 72 hours at room temperature and then dry the mixture in a vacuum, wash it with a small amount of water, recrystallize the residue from ethylene chloride and obtains 0.8 g (64% of theoretical yield) N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Melting point: 248-249°C (decomposition). Analogically, a) 4-hydroxy-2-methyl-N-phenyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide is prepared from 4-hydroxy-N-phenyl-2H-naphtho 1,1-dioxide [2,l-e -l,2-thiazine-3-carboxamide and methyl iodide. Melting point: 273-274°C (decomposition). 15 20 25 30 35 40 45 50 55 60107 647 21 22 b) N^(3-bromophenyl)-4-hydroxy-2-methylq-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(3-bromophenyl)-4-hydroxy-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide and iodine-kga-methyl. Melting point: 268-269°C (decomposition), c) N-(2-fluorophenyl)-4-hydroxy-2-methyl-ZH-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(2-fluorophenyl)-4-hydroxy-2H-1,1-dioxide naphtho[2,l-e)-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 240-243°C (decomposition), d) N-(3-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(3-fluorophenyl)-4-hydro-1,1-dioxide ksy-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 278-279°C (decomposition), e) N-(4-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(4-fluor'ophenyl)-4-hydroxy-1,1-dioxide -2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and jbd-ku methyl. Melting point: 284-285°C (decomposition), f) 4-hydroxy-2-methyl-N-(3-tolyl)-2H-naphtho[2jl-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 4-hydroxy-N-(3-tolyl)-2H-naphtho[2,l-e]- thiazine-3-carboxamide and methyl iodide. Melting point: 240-242°C (decomposition), g) 1,1-dioxide 4-hydroxy-N-(2-methoxyphenyl)-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide from 1,1-dioxide 4-hydroxy-N-(2-methoxypheny- 1)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 198—200°C, h) 4-hydroxy-N-(3-methoxyphenyl)-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 4-hydroxy-N-(3-methoxyphenyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide and methyl iodide. Melting point: 242-244°C (decomposition), ¦ , i) 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 4-hydroxy-N-(2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 237-238°C (decomposition) -2-pyridyl)-2H-naphthoJ2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 221°C (decomposition), -2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 221-223°C (decomposition), 1) 4-hydroxy-N-(3^hydroxy-2-pyridyl)-2*-mctyl-2H-naphtho[2,1-e]-1,2-thiazine-^-carboxamide 1,1-dioxide 4-hydroxy-N-(3-hydroxy-2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 255°C (decomposition), m) 4-hydroxy-2-methyl-N-(3-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 4-hydroxy-N-(3-pyridyl)-2H-naphtho 1,1-dioxide [2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide Melting point: 254°C (decomposition), n) 4-hydroxy-2-methyl-N-(4-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3^carboxamide 1,1-dioxide with 1,1-dioxide 4-hydroxy-N-(4- pyridyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide. Melting point: 257°C (decomposition) [2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 245°C (decomposition), p) N-(6-chloro-2-pyrazine,nyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 1,1-dioxide N-(6-chloro-2-pyraz- nyl)-4-hydroxy-r2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide Melting point: 209-210°C (decomposition), q) 1,1-dioxide N-(6-chloro-3-pyridazinyl)-4- hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide from 1,1-dioxide N-(6-chloro-3-pyridazinyl)-4-hydroxy-2H-naphtho[2,l-e]-li2-thiazine-3-carboxamide and methyl iodide. Melting point: 235-237°C (rqzclade),v r) N-(6-chloro-4-pyrimidinyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carbotasyamide 1,1-dioxide from N-(6-chloro-4-pi- rimidinyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 263°C (decomposition). Example XLVII. 4-Hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide To a suspension of 1.12 g (3 mmol) of 4-hydroxy-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide, 50 ml of methanol and 1.7 g (12 mmol) of methyl iodide is added dropwise 3.15 ml of sodium hydroxide (3.15 mmol), whereupon a reddish solution is formed. The mixture is stirred for 72 hours at room temperature and concentrated in vacuo to dryness. The residue is triturated with water, filtered off and recrystallized from ethylene chloride. 0.47 g (40.5% of theoretical yield) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide are obtained. Melting point: 249-250°C (decomposition). The following compounds are prepared analogously: a) 4-hydroxy-2-methyl-N-(4-methyl-2-thiazolyl)-2H-naphtho-[2,l-e]-1,2-thiazine-3-carboxamide vz 4-hydroxy-N-(4-methyl-2-thiazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide and methyl iodide. Melting point: 177°C (decomposition), b) N-(4-ethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(4-ethyl-2-thiazolyl)-4- hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 194-195°C. 4-hydrotsy-N-(5-methyl-2-thiazolyl)-2H-naphtho[2,l-e]-1,2-thiazino^3-carbo- 15 20 25 30 35 40* 45 50 55 10107 647 2* 24 xamide and methyl iodide. 249—250°C (decomposition), d) 1,1-dioxide N-(5-ethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide from N-(5-ethyl-2-thiazolyl)-4-1,1-dioxide hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 230°C (decomposition), e) N-(4,5-dimethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(4,5-dimethyl- -2-thiazolyl)-4-hydroxy-2HTnaphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 264-265°C (decomposition), f) N-(4-ethyl-5-methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(4-ethyl-5-me- tyl-2-thiazolyl)-4-hydrfoxy-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 23°-234°C (decomposition), g) N-(5-ethyl-4-methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from N-(5-ethyl-4-me- tyl-2-thiazolyl)-4-hydroxy-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 253-255°C (decomposition), h) N-(2-benzothiazolyl)-4-hydroxy-2-methyl-2H-naphtho-[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide N-(2-benzothiazolyl)-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 262°C (decomposition) -N-(4,5,6,7-tetrahydro-2-benzothiazolyl)-2H-naphtho[2,l- -e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 255-257°C (decomposition), j) N-(5,6-dihydro-7H-thiopyrano[4,3-d]thiazol-2-yl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 1,1-dioxide N-(5,6-dihydro-7H-thiopyrano[4,3-d]thiazol-2-yl)-4-hydroxy-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 2559C (decomposition), . k) 4-hydroxy-2-methyl-N-(3-methyl- lo-5-isothiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide from 4-hydroxy-N-(3-methyl-5-isothiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide and methyl iodide. Melting point: 268°C (decomposition), 1) 4-hydroxy-2-methyl-N-(1,3,4-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 4-hydroxy-N-(1,3,4-thiadiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 217-219°C (decomposition), m) 4-hydroxy-2-methyl-N-(5-methyl-1,3,4-thiadiazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 4-hydroxy-N-(5- methyl-1,3,4-thiadiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide and methyl iodide. Melting point: 252-255°C (decomposition) n) 4-hydroxy-2-meityl-N-(5-methyl-3-isoxazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 4-hydroxy-N-(5-methyl-3-isoxazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3^-carboxamide and methyl iodide. Melting point: 253°C (decomposition). 5 Example XLVIII. 2-ethyl-4-hydroxy-N-phenyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example I from 4-hydroxy-N-phenyl-2H-naphtho[2,l-e] 1,1-dioxide -e]-1,2-thiazine-3-carboxamide and ethyl iodide with a yield of 52% of the theoretical yield. Melting point: 245-247°C. Example 4-Hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide, sodium salt. To a suspension of 1.94 g (5 mmol) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide in 30 ml of methanol is added a solution of 0.2 g (5 mmol) of sodium hydroxide in 20 ml of methanol and left to stand for 24 hours at room temperature. The reaction mixture is evaporated and treated with ether. The crystals are filtered off and dried in vacuo. 1.9 g (93% of theoretical yield) of product are obtained, melting point: 230°C (decomposition). Example L. Sodium salt of 1,1-dioxide 4-hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-na- phto[2,1-e]-1,2-thiazine-3-carboxamide 1.9 g (4.8 mmol) 4-hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-naphtho(2,1-e)-1,2-thiazine-3-carboxamide 1,1-dioxide; is added to the solution 0.192 g (4.8 mmol) of sodium hydroxide in 75 ml of methanol. The reaction mixture is stirred for 3 hours at 00°C, concentrated and treated with ether. The crystals are filtered off and dried in vacuo: 2.0 g (99.7% of theory). Melting point: decomposes at 218-220°C. Example 11. Cyclohexylamine salt of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-azine-3-carboxamide 1,1-dioxide. Example 11. N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide For 2-me- 45 acid chloride 1,1-dioxide solution tyl-4-(i-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid in tetrahydrofuran,* obtained by reacting 0.63 g (2 mmol) of 1,1-dioxide 2-methyl-4-(l-pyrrolidinyl)-2HTnaphtho[2,l-e]rl,2-thiazine zH),25 g (2.5 mmol) phosgene and 0.25 g (2.5 mmol) triethylamine in 16 ml anhydrous tetrahydrofuran, a solution of 0.51 g (44 mmol) of 3-chloroaniline in 8 ml of dry tetrahydrofuran is added dropwise at -40°C. The reaction mixture is allowed to reach room temperature over 6 hours and then stirred for 24 hours at this temperature, then added with ice-cold water and extracted twice with methylene chloride. The organic phase is then washed twice with water, dried over sodium sulfate and concentrated in a vacuum. The residue is treated with petroleum ether to give crude crystalline N-(3-chlorophenyl)-2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide (mp: 163-167°C with decomposition), which is immediately dissolved in 6 ml of glacial acetic acid and treated with 2 ml of 2N hydrochloric acid. The mixture is heated to 100°C for 30 minutes and, after cooling, 50 ml of ice-cold water are added. The precipitated product is filtered off, dried and recrystallized from ethylene chloride/petroleum ether. 410 mg (49% of theoretical yield) of N-(3-chlorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide are obtained. Melting point: 247-248°C (decomposition). The starting compound is synthesized as follows: a) 2-methyl-4-(i-pyrrolidinyl)-2H-naphtho[2,l-e]-l,2-thiazine 1,1-dioxide 6.6 g (0.025 mol) 2-Methyl-2H-naphtho[2,1-e]-1,21thiazin-4(3H)-one 1,1-dioxide, 3.6 g (0.050 mol) of pyrrolidine and 0.1 g of p-toluenesulfonic acid are dissolved in 150 ml of benzene and heated to reflux for 72 hours using a separator. water under reflux. The cooled reaction solution is washed with water neutral reaction, drought and synthesis. 5.8 g (74% of the theoretical yield) of 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine 1,1-dioxide crystallize. Melting point: 176-178°C. b) 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide To a solution of 0.25 g (2.5 mol) of phosgene (1.3 ml of a 20% solution in toluene) in 4 ml, cooled to -40°C anhydrous tetrahydrofuran, also added cooled to the temperature A solution of 0.63 g (2 mmol) of 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-1,1-dioxide and 0.25 g (2.5 mmol) of triethylamine in 12 ml of anhydrous tetrahydrofuran was prepared at -40°C. The reaction mixture was allowed to reach room temperature within 1 hour and then left at room temperature for 2 hours. The enamino acid chloride obtained as a tetrahydrofuran solution was used directly for the further reaction. Example 83: 4-Hydroxy-2-methyl-N-phenyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide-1,1-dioxide was prepared analogously to Example 1 from 2-Methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and aniline. Melting point: 273-274°C (decomposition). Analogously to Example LII, the following is also prepared: m a) N-(3-bromophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl-acid 1,1-dioxide -4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 3-bromoaniline. Melting point: 268—269°C (decomposition), b) N-(2-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl-4-(l- -pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-fluoroaniline. Melting point: 240-243°C (decomposition), c) N-(3-fluorophenyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxyamide 1,1-dioxide from 2-methyl-4-(1-pyrrolide- nyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid and 3-fluoroaniline. Melting point: 278-279°C (decomposition) from xylene, 6 d) 1,1-dioxide N-(4-fluorophenyl)-4-hydroxy-2- methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide from 2-methylio-4-(1-4-irolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic chloride 1,1-dioxide and 4-fluoroaniline. Melting point: 248-10,285°C (decomposition) from xylene, e) 1,1-dioxide 4-hydroxy-2-methyl-N-(3-tolyl)-2H-naphtho-[2,l-e]-1,2-thiazine-3-carboxamide from 2-methyl-4-(pyrrolidinyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and m-toluidine. Melting point: 240-242°C (decomposition) from xylene, f) 4-hydroxy-N-(2-methoxyphenyl)-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-me-20 acid chloride 1,1-dioxide tyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-methoxyaniline. Melting point: 198-200°C from the system ethylene chloride/petroleum ether, g) 4-hydroxy-N-(3-methpoxyphenyl-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride and 3-methoxyaniline. Melting point: 242-244°C (decomposition) from xylene. 80 h) 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl-4-(l-pyro- lidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-pyridine, Melting point: 85 237-238°C (decomposition), i) 1,12-dioxide 4-hydroxy-2-methyl-N-(4-methyl- lo-2-pyridyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide from 1,1-dioxide chloride 2-methyl-4-(l-pyrrolidinyl)-2H-naphtho[2,l-e]-l,2-thiazine-3-4i carboxylic acid and 2-amino-4-methyl-pyridine, Melting point: 221°C (decomposition), j) 1,1-dioxide 4-hydroxy-2-methyl-N-(6-methyl- 1-2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide from 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and 2-amino-6-methyl-pyridine. Melting point: 221-223°C (decomposition), k) 4-hydroxy-N-(3-hydroxy-2-pyridyl)-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-car- 5P boxamide 1,1-dioxide from 2-me- acid chloride 1,1-dioxide tyl-4-(l-pyrrolidinyl)-2H-naphtho[2,l-e]-l,2-thiazine-^-3-carboxylic acid and 2-amino-3-hydroxypyridine. Melting point: 255°C (decomposition), 1) 1,1-dioxideSk 4-hydroxy-2-methyl-N-(3-pyrr-re dylo)-2H-naphtho[2,1-6]-1,2-thiazine-3-carboxamide from 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and 3-amino-pyridine. Melting point: 254°C (decomposition) from ethanol/ethyl acetate, 50 m) 4-hydroxy-2-methyl-N-(4-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from acid chloride 1,1-dioxide 2-methyl-4-(l-pyry-' dynyl)-2H-naphtho[2,1-e]-1,2-i;iazine-3-carboxylic acid and 4-amino-pyridine. Melting point; 55 257°C (decomposition) - from ethanol*107 647 27 28 n) N-(6-chloro-3^pyridazinyl)-4- hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3- carboxamide 1,1-dioxide from 2-acid chloride methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 3-amino-6-chloro-pyridazine. Melting point: 235-237°C (decomposition), * o) 4-hydroxy-2-methyl-N-pyrazinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-ka:boxamide 1,1-dioxide from 2^methyl-4-(1-pyro^) acid chloride 1,1-dioxide lidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and amine-pyrazine. -Melting point: 245°C (decomposition), p) N-(6-chloro-2-pyrazinyl)-4-hydroxy-2-methyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from, 2-me- tyl-4-(l-pyrrolidinyl)-2H-naphtho[2,l-e]-l,2-thiazine-3-carboxylic acid and 2-amino-6-chloro-pyrazine. Melting point: 209-210°C (from ethanol), q) 1,1-dioxide N-(6-chloro-4-pyrimidinyl)-4- hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazirio-3-carboxamide from 2-methylp-4r(1-pyrrolidinyl)-2H-naphthot2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and 4-amino-6-chloro-pyrimidine. Melting point: 263°C (decomposition) with xylene. Example LIV. 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,l-e]-12-thiazine-3-carboxamide 1,1-dioxide ' To a solution of 6.4 mmol) 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]- -1,2-thiazine-3-carboxylic acid, which is obtained by reacting 2.0 g (6.4 mmol) of 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]1,2-thiazine 1,1-dioxide with 4 ml of a 20*/« solution of phosgene in toluene (7.7 mmol) in the presence 0.78 g (7.7 mmol) triethylamine in 80 ml of tetrahydrofuran, a solution of 0.9 g (9 mmol) 2-aminotriazole and 0.78 g (7.7 mmol) triethylamine in 8 ml of tetrahydrofuran is added dropwise at -40°C. The reaction mixture is first brought to room temperature over 2 hours, then stirred for 36 hours at room temperature, then water is added and the mixture is shaken several times with ethylene chloride. The organic phase is evaporated, the residue is heated under reflux with 2 N hydrochloric acid for 2 hours. After cooling, it is extracted with ethylene chloride, the organic phase is evaporated, and the residue is purified by chromatography on silica gel using chloroform/methanol. (volume ratio 10:1) as eluent. From the eluates, 0.9 g (35% of theoretical yield) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide is obtained, melting point: 248-249°C (decomposition). Analogously, the following is prepared: * a) 4-hydroxy-2-methyl-N-(4-methyl-2-thiazolyl)-2H-naphtho[2^1-e]-1,2-thiazyTio*-8-taffboxamide 1,1-dioxide from 2-methyl acid chloride 1,1-dioxide 1-4-(1-pyrrolidinyl)-2H*naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-4-methyl-thiazoyl. Melting point: 177°C, b) N-(4-ethyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carbpoxyanlide 1,1-dioxide from 2-methyl-4-acid chloride 1,1-dioxide -(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxyl and 2-amino-4-ethyl-thiazole. Melting point; .194-195°C, c) 4-hydroxy-2-melyl-N-(5-methyl-2-thiazole)-2H-naphyto[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl acid chloride 1,1-dioxide 1-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-5-methyl-thiazole. Melting point: 249-250°C (decomposition) from xylene, d) N-(5-ethyl-2^;iazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from acid chloride 2-methyl-1-4-(1-pyrrolidinyl)-2H-naphtho{2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-5-ethyl-thiazole. Melting point: 230°C (decomposition) from xylene, e) N-(4,5-dimethio-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-acid chloride methyl-4-(1-pyrrolidinyl)-2H-naphtho(2,1-e)-1,2-thiazine-3-carboxylic acid and 2-amino-4,5-a*wumethyl-thiazole. Melting point: 264-265°C (decomposition) from ethylene chloride, f) N-(4-ethyl-5-methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-acid chloride 1,1-dioxide methyl-4-(1-pyrrolidinyl)-2H^naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-4-ethyl-5-methyl-thiazole. Melting point: 233-234°C (decomposition) from xylene, g) N-(5-ethyl-4-methyl-2-thiazolyl)-4-hydroxy-2-methyl-2H-naphtho[2,1-e]-1,2-thiazine-3-carichydroxyamide 1,1-dioxide from acid chloride 1,1-dioxide 2-methyl-4-(1-pyrrolidinyl)-2H-riafto[2,1-e]-1,2-thiazine-3-carboxylic acid and 2-amino-5-ethyl-4-methyl-thiazole. Melting point: 253-255°C (decomposition) from ethanol, h) N-(2-benzothiazolyl)-4-hydroxy-2-methyl-2HTnaphtho{2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl-acid chloride 1,1-dioxide -4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylate and 2-amino-benzothiazole. Melting point: 262°C (decomposition) from xylene. i) 4-hydroxy-2-methyl-N-(4,5,6,7- -tetrahydro-2-benzothiazolyl)-2H-naphthó[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl-4-(l-pyrrolidinyl)-2H- acid chloride 1,1-dioxide naphtho[2,1-e]-1,2-thiazine-3-:carboxylic acid and 2-amino-4,5,6,7-tetrahydro-benzothiazole. Melting point: 255-257°C (decomposition) from ethylene chloride, j) N-(5,6-dihydro-7H-thiopyrano[4,3-d]-thiazol-2-yl-4-hydroxy-2-methyl-2H-naphtho^[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-methyl*4-(1-pyrrolidinyllp2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride and 2-amino-5,6-dihydro-7H-thiopyrano[4,3-d]-thiazole chloride 1,1-oxide. Melting point: 255°C decomposition) with xylene, k) 1,1-dioxide 4-hydroxy-2-methyl-N-(3-methyl-5-isothiazolyl)-2H-naphtho[2,l-e}-1,2-thiazine-3-carboxamide from 2-methyl-4-(l-pyrrolidinyl)-2H-naphtho[2,l-e]-l,2-thiazine-3-acid chloride 1,1-dioxide -carboxylic acid, and 5-amino-3-methyl-isothiazole. Melting point: 268°C (decomposition) from ethyl chloride, 1) 1,1-dioxide 4-hydroxy-2-methyl-N-(1,3,4-thia-diazolyl)-2H-naphtho[2,l-e1-l,2-thiazine-3-carboxy- ifi 15 20 25 30 3B 50 55 60107 647 29 3e amide from 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and 2-amino-1,3,4-thiadiazole. Melting point: 217-219°C (decomposition) from the system ethylene chloride/ethyl acetate, m) 1,1-dioxide 4-hydroxy-2-methyl-N-(5-methyl*1,3,4-thiadiazol-2-yl)-2H-naphtho[2,1-e]-1,2-thiazy- no-3-carboxamide from 2-methyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid chloride 1,1-dioxide and 2-amino-5-methyl-1,3,4-thiadiazole.* Melting point: 252-255°C (decomposition) from ethanol, n) 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide from 2-me- acid chloride 1,1-dioxide tyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine-3--carboxamide and 3-amino-5-methyl-isoxazole. Melting point: v253°C. Example LV. 2-ethyl-4-hydroxy-N-phenyl-2H-naphtho[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. Prepared analogously to Example I' from 1,1-dioxide 2-ethyl-4-(1-pyrrolidinyl)-2H-naito[2,1-e]-1,2-thiazine-3-carboxylic acid chloride and aniline with a yield of 46% of the theoretical yield. Melting point: 245-247°C \ ethylene/petroleum ether system. The starting compound is produced in a multi-stage process: a) 1,1-dioxide f-ethyl-4 -(1- pyrrolidinyl)- 2H- naphtho[2,l-e]-l,2-thiazine 2 g (7.3 mmol) 1,1-dioxide 2-ethyl-2H-naphtho[2,1-e]-1,2-thiazin-4(3H)-one, 1.04 g (14.6 mmol) of pyrrolidine and 200 mg of p-toluenesulfonic acid in 400 ml of benzene are heated to reflux using a water separator for 24 hours. Then a further 1.04 g (14.6 mmol) of pyrrolidine and 200 mg of p-toluenesulfonic acid are added and the reaction mixture is heated again in the same way for 24 hours. After cooling, the reaction mixture is concentrated and extracted several times with ether. The combined ether extracts are washed twice with water, dried and concentrated. After recrystallization from methanol, 1.2 g (50% of theoretical yield) of the desired enamine are obtained. Melting point: 115-117°C. b) 2-ethyl-4^(1-pifoli- dynyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid. It is prepared analogously to "example LV under b) from 2-ethyl-4-(1-pyrrolidinyl)-2H-naphtho[2,1-e]-1,2-thiazine 1,1-dioxide and phosgene in the form of a solution in tetrahydrofuran °5 g (1.5 mmol) 4-Hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide is suspended in 10 ml of methanol and 0.15 g (1.5 mmol) of cyclohexylamine is added. The resulting solution is highly concentrated in vacuo and the residue is triturated with acetone. The obtained crystals are filtered off and washed with a small amount of acetone and ether. 0.55 g (76% of theory) of crystals are obtained, melting point: 205-207°C. Example 66: Sodium salt of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide -hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-B]-, -1,2-thiazine-3-carboxamide. To a suspension of 1.94 g (5 mmol) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-, -1,2-thiazine-3-carboxamide-1,1-dioxide in 30 ml of methanol was added a solution of 0.2 g (5 mmol) of sodium hydroxide in 20 ml of methanol and left for 24 hours at room temperature. The reaction mixture was evaporated and ether was added. The crystals were filtered off and dried in vacuo. 1.9 g (93% of theory) of product was obtained, melting at 230°C (decomposition). Example LVII. 4-Hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide sodium salt 1.9 g (4.8 mmol) of 4-hydroxy-2-methyl-N-(4-methyl-2-pyridyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide are treated with a solution of 0.192 g (4.8 mmol) of sodium hydroxide in 75 ml of methanol. The reaction mixture is stirred for 3 hours at 30°C, concentrated, and treated with ether. The crystals are filtered off and dried in vacuo: 2.0 g (99.7% of theory). melting point: decomposition at 218-220°C. Example LVIII. Cyclohexylamine salt and 4-hydroxy-2-methyl-Nr(2-thiazolyl)-2H-naito[2,l-e]-1,2-thiazine-3-carboxamide 1,1-dioxide. 0.5 g (1.5 mmol) of 4-hydroxy-2-methyl-N-(2-thiazolyl)-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide is suspended in 10 ml of methanol and 0.13 g (1.5 mmol) of cyclohexylamine is added. The resulting solution is highly concentrated in vacuo and the residue is triturated with acetone. The obtained crystals are filtered off and washed with water 1. A method for preparing new 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxides of the general formula I, wherein R1 is a hydrogen atom or a methyl group and Ar is a phenyl, 2-pyridyl, 2-pyrazinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 2-benzothiazolyl or 5-methyl-3-isoxazolyl group, and their salts with inorganic or organic bases, characterized in that 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid ester 1,1-dioxide of the general formula 2, wherein R 8 is an alkyl group having 1-6 carbon atoms and R 1 has the meaning given above, is reacted with an aromatic amine of the general formula 3, wherein Ar has the meaning given above, at a temperature of 60-200°C in an inert organic solvent and the resulting compound of the general formula 1 is optionally converted into a salt with an inorganic or organic base. 2. A process according to claim 1, characterized in that aromatic hydrocarbons, dimethylformamide, dimethylacetamide, dimethylsulfoxide, hexamethylphosphoric acid triamide, an ether or a peroxymonosulfonic acid are used as the inert organic solvent. 3. A method for preparing new 4-hydroxy-2H-[(2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxides of the general formula 1, wherein R1 is a methyl group and Ar is a phenyl, 2-pyridyl, 2-pyrazinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 2-benzothiazolyl or 5-methyl-3-isoxazolyl group, and their salts with inorganic or organic bases, characterized in that 1,1-Dioxide-4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxyamine of the general formula 4, wherein Ar has the meaning given above, is reacted with a methyl halide in the presence of a base at a temperature of 0°C to 80°C and the resulting compound of the general formula 1 is optionally converted into a salt with an inorganic or organic base. 4. A process according to claim 3, characterized in that alkali metal or alkaline earth metal hydroxides or carbonates, alkali metal or alkaline earth metal alkoxides or tertiary amines are used as bases, and water, alcohols or mixtures thereof are used as solvents. 5. A process according to claim 3, characterized in that aliphatic 6. A process according to claim 3, characterized in that alkali metal or alkaline earth metal hydrides in aromatic hydrocarbons or in an open-chain or cyclic ether as solvent are first reacted with the compound of general formula 4, and then an alkyl halide is added. 7. A process for the preparation of new 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxides of general formula 1, wherein R1 is a methyl group and Ar is a phenyl, 2-pyridyl, 2-pyrazinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 2-benzoitazolyl or 5-methyl-3-isoxazolyl and their salts with inorganic or organic bases, characterized in that an enamino acid chloride of the general formula 6, in which Hal is a halogen atom and R< and R1 are an alkyl group with 1-3 carbon atoms or together with the nitrogen atom between them represent a piperidine, pyrrolidine, morpholino or N-methylpiperazine group, is reacted with an aromatic amine of the general formula 3, in which Ar has the above-mentioned meaning, in an inert organic solvent, at a temperature of 0-80°C, in the presence of a tertiary organic base to give an enaminocarboxamide of the formula 6a, which is hydrolyzed in an acidic medium and the obtained compound of general formula I is optionally converted into a salt with an inorganic or organic base. 8. A process according to claim 7, characterized in that the hydrolysis of the enaminocarboxamide is carried out using aqueous or aqueous-alcoholic solutions of strong organic or inorganic acids. 9. A process according to claim 7, characterized in that the reactions to obtain the enaminocarboxamide of general formula VIa are carried out in an aromatic hydrocarbon or in an ether in the presence of a tertiary organic base. 10. A process according to claim 7, characterized in that the hydrolysis of the enaminocarboxamide is carried out using aqueous or aqueous-alcoholic solutions of strong organic or inorganic acids. 11. A process for the preparation of new 1,1-dioxides 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamides of general formula 1, in which Ri is a hydrogen atom or a methyl group, Ar is a 3-chlorophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl group, 3-tolyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methyl-2-pyridyl, 6-methyl-2-pyridyl, 3-hydroxy-2-pyridyl, 3-pyridyl, 4-pyridyl, 6-chloro-3-pyridinyl, 6-chloro-2-pyrazinyl, 6-chloro-4-pyrimidinyl, 4-ethyl-2-thiazolyl, 5-methyl-2-thiazolyl, 5-ethyl-2-thiazolyl, 4-ethyl-5-methyl-2-thiazolyl, 5-ethyl-4-methyl-2-thiazolyl, 4,5,6,7-tetrahydro-2-benzothiazolyl, 5,6- dihydro-7H-thiopyrano[4,3-d]-thiazolyl', 3-methyl-5-isothiazolyl, 1,3,4-thiadiazolyl or 5-methyl-1,3,4-thiadiazolyl-2, Ri may also denote an ethyl group, in which case Ar may also denote a group in addition to the values given above phenyl, 2-pyridyl, pyrazinyl, 2-thiazolyl, 4-methyl-2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 2-benzothiazolyl or 5-methyl-3-isoxazolyl esters and their physiologically acceptable salts with inorganic or organic bases, characterized in that 1,1-dioxide of the ester of 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxylic acid of the general formula II, wherein R1 has the meaning given above and R8 is an alkyl group with 1-6 carbon atoms or an aralkyl group with 7-10 carbon atoms, is reacted with an aromatic amine of the general formula III, wherein Ar has the meaning given above, in an inert organic solvent or in an excess of the amine of the general formula III, in at a temperature of 60-200°C and the obtained compound of general formula I is optionally converted into a salt by means of an inorganic or organic base. 12. A process according to claim 11, characterized in that aromatic hydrocarbons such as dimethylformamide, dimethylacetamide, dimethylsulfoxide, hexamethylphosphoric acid triamide, an ether or an excess of an amine of formula III are used as inert organic solvents and the alcohol formed in the reaction is continuously removed. 13. A process for the preparation of new 4-hydroxy-2H-naphtho[2,1E]-1,2-thiazine-3-carboxamide 1,1-dioxides of general formula I, wherein R1 is a methyl or ethyl group and Ar* is a 3-chlorophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-tolyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methyl- -2-pyridyl, 6-methyl-2-pyridyl, 3-hydroxy- -2-pyridyl, 3-pyridyl, 4-pyridyl, 6-chloro-3-pyridazinyl, 6-chloro-2-pyrazinyl-6- 15 20 25 30 35 40 45 50 55 60107 647 33 34 -chloro-4-pyrimidinyl, 4-ethyl-2-thiazolyl, 5- -methyl-2-thiazolyl, 5-ethyl-2-thiazolyl, 4-ethyl- -5-methyl-2-thiazolyl, 5-ethyl-4-methyl-2-thiazolyl, 4,5,6,7-tetrahydro-2-benzothiazolyl, 5,6-dihydro-7H-thiopyrano[4,3-d]-thiazolyl, 3-methyl-5-isothiazolyl, 1,3,4-thiadiazolyl or 5-methyl-1,3,4-thiadiazolyl-2, R1 also denotes an ethyl group, wherein A then, in addition to the above-mentioned meanings, also denotes a phenyl, 2-pyridyl, pyrazinyl, 2-thiazolyl, 2-benzothiazolyl or 5-methyl-3-isoxazolyl group, and their physiologically acceptable salts with an inorganic or organic base, 14. A method according to claim 13, characterized in that 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxamide 1,1-dioxide of general formula 4, wherein Ar has the above-mentioned meaning, is reacted with an alkyl halide of general formula 5, wherein R' 1 is a methyl or ethyl group and Hal is a halogen atom, in the presence of a base, at a temperature of 0-80°C, and the resulting compound of general formula 1 is optionally converted into a salt with an inorganic or organic base. 15. A method according to claim 14, characterized in that alkali or alkaline earth metal hydroxides or carbonates, alkali or alkaline earth metal alkoxides or tertiary arylates are used as bases, and Water, alcohols or mixtures of these solvents are used as solvents. 15. A process according to claim 13*, characterized in that aliphatic ketones and alkali metal or alkaline earth metal carbonates are used as bases. 16. A process according to claim 13, characterized in that alkali metal or alkaline earth metal hydrides in aromatic hydrocarbons or in an open-chain ether or cyclic ether as solvent are first reacted with a compound of general formula 4 and then an alkyl halide of general formula 5 is added. 17. A process for the preparation of new 4-hydroxy-2H-naphtho[2,1-e]-1,2-thiazine-3-carboxy-1,1-dioxides amides of general formula 1, wherein R 1 is a methyl or ethyl group and Ar is a 3-chlorophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-tolyl, 2-methoxyethyl, 3-methoxyphenyl, 4-methyl-2-pyridyl, 6-methyl-2-pyridyl, 3-hydroxy-2-pyridyl, 3-pyridyl, 4-pyridyl, 6-chloro-3-pyridazinyl, 6-chloro-2-pyrazinyl, 6-chloro-4-pyrimidinyl, 4-ethyl-2-thiazolyl, 5-methyl-2-thiazolyl, 5-ethyl-2-thiazolyl, 4-ethyl-5-methyl-2-thiazolyl, 5-ethyl-4-methyl-2-thiazolyl, 4,5,6,7-tetrahydro-2-benzothiazolyl, 5,6-dihydro-7H-thiopyrano[4,3-d]-thiazolyl-2, 3-me- tyl-5-isothiazolyl, 1,3,4-thiadiazolyl or 5-methyl-1,3,4-thiadiazolyl-2, Rx also denotes an ethyl group, and then Ar, in addition to the meanings given above, also denotes a phenyl-2-pyridyl, pyrazinyl, 2-thiazolyl, 4-methyl- -2-thiazolyl, 4,5-dimethyl-2-thiazolyl, 2-benzothiazolyl or 5-ethyl-S-isoxazolyl, and their physiologically acceptable salts with inorganic or organic bases, characterized in that an enamino acid chloride of general formula 6, in which R 1 is a methyl or ethyl group, I 1 a1 is a halogen atom, R 4 and R 5 are alkyl groups with 1-3 carbon atoms or, together with the nitrogen atom between them, are piperidino, pyrrolidino, morpholino or N-methylpiperazine group, is reacted with an aromatic amine of general formula 3, in which Ar has the above meaning, in an inert solvent, at a temperature from -40 to +80°C, and the resulting enaminocarboxamide is obtained The compound of general formula 6a is then hydrolyzed with an acid to a compound of general formula 1, which is optionally converted into a salt with an inorganic or organic base. 18. The process according to claim 17, characterized in that the reaction to obtain the enaminocarboxamide of general formula 6a is carried out in an aromatic hydrocarbon or in an ether in the presence of a tertiary organic base. 19. The process according to claim 17, characterized in that the hydrolysis of the enaminocarboxamide is carried out with aqueous or aqueous-alcoholic solutions of strong organic or inorganic acids. 15 20 25 30 35 40 45107 647 CO-NH-Ar FORMULA 1 .CO-O-R3 FORMULA 2 NH2- Ar FORMULA 4 R, - Hal FORMULA 5 SO^I FORMULA 3 FORMULA 6107 647 i r soj1' ,vi FORMULA 6a .CO-NH-Ar n-r; H-N V 0^/0 rN-H FORMULA 7 O ^^^ ^N - R' FORMULA 9 R4\/\ N ^ ^ rrN - r; ir t so2 1 FORMULA 8 FORMULA 10 PL PL PL PL PL PL PL PL